读者－编者－作者

读者－编者－作者问：解释双克降压机制甚多，你觉得主要是什么机制最起作用？答：双克降压机制分近期和远期两部分来考虑，近期主要是血容量减少１０％～１５％，心搏出量下降，血压下降，长期用药血容量和心搏出量又恢复到治疗前状态，这时主要降压机制还是总血管阻力下...     

读者－作者－编者

读者－作者－编者《高血压杂志》编辑部：我是一名原发性高血压二期患者，也是《高血压杂志》的读者。近日我到南宁市中心医院作检查，发现血、尿β２微球蛋白（β２－Ｍ）均明显增高（血β２－Ｍ２．２ｎｇ／Ｌ，该院正常值＜１．９５ｎｇ／Ｌ；尿β２－Ｍ１．１５ｎｇ／...     

SS／GHRH－GH－IGF－Ⅰ轴与糖尿病

ＳＳ／ＧＨＲＨ－ＧＨ－ＩＧＦ－Ⅰ轴与糖尿病廖二元，许樟荣胰岛素样生长因子（ｉｎｓｕｌｉｎ－ｌｉｋｅｇｒｏｗｔｈｆａｃｔｏｒｓ，ＩＧＦｓ）为一组分子量约７５００Ｄａ的蛋白质激素，分ＩＧＦ－Ⅰ和ＩＧＦ－Ⅱ两种，现已查明，ＩＧＦ－Ⅰ即生长介素Ｃ。垂体分泌的...     

Distribution and anti－HBV effects of antisense oligodeoxynu－deotides conjugated to galactosylated poly－L－lysine

AIM: To describe distribution of the phosphorothioated antisense oligodeoxynucleotides (PS-asODNs) conjugated to galactosylated poly-L-lysine (Gal-PLL) in mice, and to observe their effects on expression of HBV gene in the 2.2.15 cells and transgenic mice.METHODS: According to the result of direct sequencing of PCR amplified products, a 16 mer phosphorothioate analogue of the antisense oligodeoxynucleotides (PS-asODNs) directed against the HBV U5-like region was conjugated to the hepatotropic Gal-PLL molecules. Its distribution was demonstrated using asODNs labeled with ^32p at the 5‘ terminus with a T4-polynucleotide Kinase. Its inhibition effect on HBV expression was observed in the transfected 2.2.15 cells and transgenic mice.RESULTS: The Gal-PLL and asODNs could form stable complex at a molar ratio of 2:1. As shown in the HBV-transfected 2.2.15 cells, the inhibition effects of asODNs alone and asODNs conjugated to Gal-PLL, at 10μmol/L for both, on HBsAg and HBeAg production were different,the former being 70 % and 58 %, respectively, and the latter being 96 % and 82 %, respectively. A more pronounced reduction was also observed in viral DNA load in the culture supernatant for the test with Gal-PLL-asODNs. Among many mouse organs, livers retained more asODNs molecules after administration. The preferential concentration in liver was found to be 52.14 % for Gal-PLL-asODNs, as high as 2.38-fold of that for asODNs (21.9 %). Both elements decreased gradually in liver, with 2.9 % of the former, 5.99 % of the latter retained 24 hours after the administration. The injection interval, therefore, was recommended to be 24 hours. In the transgenic mice, serum HBsAg decreased significantly (P<0.01) at the 12th day after administrating Gal-PLL- asODNs, the serum HBV DNA turned negative in 4 of the 6 mice.CONCLUSION: Antisense oligodeoxynucleotides conjugated to Gal-PLL can be concentrated in liver and intaked by hepatocytic cells. This may result in specific inhibition of expression and replication of HBV in vitro and in vivo.     

老年NIDDM患者尿液N－乙酰－β－D－氨基葡萄糖苷酶变化的临床评价

对９６例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者尿液Ｎ－乙酰－β－Ｄ－氨基葡萄糖苷酶（ＮＡＧ）的变化作了临床研究。结果显示：老年患者（６２例）尿液ＮＡＧ排出量（３２．２０±３．８０Ｕ／ｇ·Ｃｒ）高于健康对照组（３２例，７．０１±０．４２Ｕ／ｇ·Ｃｒ）及非老年患者（３４例，１８．８３±２．５７Ｕ／ｇ·Ｃｒ）（Ｐ均＜０．０１）。其增高程度与蛋白尿、糖尿病病程、视网膜微血管病变关系密切。对老年糖尿病患者尿ＮＡＧ水平的观察可作为识别是否合并早期糖尿病肾病的指标之一。     

胃－空肠－结肠瘘二例

胃－空肠－结肠瘘二例房淑霞，韩瑞华，黄象谦［例１］患者男性，４２岁。于２年前因十二指肠球部溃疡穿孔，行胃大部切除，ＢⅡ式手术。１年后无明显诱因出现腹泻，每日３～４次，黄色，不成形。有时进食后很快以食物原形排出。无反酸、恶心、呕吐，无脓血便及黑便，无腹...     

呈P－P~－－QRS图形的房性反复搏动1例

呈Ｐ－Ｐ~－－ＱＲＳ图形的房性反复搏动１例许粤燕（广东省韶关市第一人民医院心电图室韶关５１２０００）临床资料及心电图分析患者女性，７５岁，临床诊断：脑梗塞。附图为入院常规心电图的ＩＩ导联。Ｐ１、Ｐ２为期前Ｐ波，Ｒ－Ｐ１＝０．２２ｓ，Ｒ－Ｐ２＝０．１９?..     

高血压病尿N－乙酰－β－D氨基葡萄糖苷酶活性、β_2－微球蛋白变化及其临床意义

采用放射免疫法测定了１６３例高血压病人的尿Ｎ－乙酰－β－Ｄ氨基葡萄糖苷酶（ＮＡＧ）活性和β２－微球蛋白（β２－ＭＧ）。结果表明：①高血压及老年高血压组的尿ＮＡＧ和β２－ＭＧ均高于对照组，临界高血压组与对照组比较无显著差异。②较之对照组，高血压组及老年高血压组之间的ＮＡＧ活性增高的人数比率（４４．４７％、８８．９３％）和β２－ＭＧ增高的人数比率（４６．５３％、６９．４５％）有显著差异，两组中各自的ＮＡＧ活性槽高的人数比率与尿β２－ＭＧ增高的人数比率之间的比较差异无显著意义。③经治疗血压降至正常，增高的尿ＮＡＧ活性逐渐下降，约１０周达到正常范围，但β２－ＭＧ在降压２１周后还没有显示下降趋势。以上结果提示：高血压Ⅰ期肾小管就可能受到损害；年龄增加，高血压病人的肾小管受损有增多趋势；尿ＮＡＧ活性与β２－ＭＧ在表现高血压肾小管早期损害方面有一致的临床意义，但降压后在显示肾小管的预后方面两者有着不同的意义。     

IFN－γ联合rhTNF－α抑制白血病细胞c－myc原癌基因的表达

将干扰素（ＩＦＮ－ｒ）和肿瘤坏死因子（ＴＮＦ－α）与人白血病细胞株及急性髓细胞白血病（ＡＭＬ）病人原代白血病细胞体外液相共育，用细胞，总ＲＮＡ样品与￣（３２）Ｐ标记的ｃ－ｍｙｃＤＮＡ探针打点杂交，我们观察了ＩＦＮ－ｒ联合ＴＮＦ－α作用ＨＬ－６０细胞，ＴＮＦ作用病人原代白血病细胞对其ｃ－ｍｙｃ癌基因表达的影响。结果发现：１００Ｕ／ｍｌ和５００Ｕ／ｍｌ的ＩＦＮ－ｒ可明显促进５０Ｕ／ｍｌＴＮＦ－α对ＨＬ－６０细胞ｃ－ｍｙｃ表达的抑制作用；８例ｃ－ｍｙｃ高表达的ＡＭＬ病人，经５０Ｕ／ｍｌＴＮＦ作用后，其ｃ－ｍｙｃｍＲＮＡ水平发生显著性减低。结果证明了ＩＦＮ－ｒ具有协同ＴＮＦ－α抑制ＨＬ－６０白血病细胞ｃ－ｍｙｃ癌基因表达的作用，ＴＮＦ－α对白血病细胞株及病人原代白血病细胞ｃ－ｍｙｃｍＲＮＡ水平均有明显的抑制效应。     

抗－HBc－IgM试剂盒临床使用评价

抗－ＨＢｃ－ＩｇＭ试剂盒临床使用评价郑怀竞，王文丽卫生部临床检验中心于１９９１年７月受卫生部新药审评办公室委托，对抗－ＨＢｃ－ＩｇＭ试剂盒进行临床使用评价。卫生部临床检验中心在１９９１年以前，通过乙型肝炎病毒标志物检验室间质评，了解到该试剂盒假阳性率...     

LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma

AIM： To analyze the expression profiles of a human gastriccancer-related gene, GCRG123, in human gastric signetring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123.
METHODS： In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information （NCBI） and the University of California Santa Cruz （UCSC） databases were used for the analyses.
RESULTS： The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons （LINE-1, L1）. BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and -23 of Rb, 5＇ flanking region of IL-2 and clotting factor Ⅸ genes.
CONCLUSION： GCRG123, an active member of the Lt family, was up-regulated in human gastric signet-ring cell carcinoma.     

抗人胃癌相关蛋白GCRG213多克隆抗体的制备鉴定及初步应用

目的 制备胃癌相关蛋白GCRC213的多克隆抗体. 方法在大肠杆菌中表达Thioredoxin/GCRG213融合蛋白,并以所获蛋白免疫新西兰白兔,制备兔抗GCRG213的抗体.酶联免疫吸附测定(ELISA)、Western blot法鉴定抗体的效价及特异性.免疫组化染色观察GCRG213在胃癌和止常组织中的表达. 结果在大肠杆菌中高效表达出相对分子质量(Mr)约为29 400的thioredoxin/GCRG213融合蛋白,经凝胶回收法得到纯度近100%的蛋白产品.制备兔抗GCRG213抗体.ELISA法检测抗体的效价达到1:256 000.Western blot证实该抗体可与原核表达的GCRG213蛋白特异性结合.免疫组化染色显示GCRG213在胃癌组织中的表达明显强于正常胃黏膜组织. 结论兔抗GCRG213抗体的成功制备,为进一步研究GCRG213的牛物学功能及其在胃癌发牛发展中的作用奠定了基础.     

胃癌相关基因GCRG213正反义真核表达载体的构建及鉴定

目的:构建胃癌相关基因GCRG213正、反义真核表达载体．方法:从pGEM-T质粒上扩增出的胃癌相关基因GCRG213的DNA片段,两端分别引入限制性内切酶KpnI,BamHI和EcoRI, BamHI识别位点．按正向、反向克隆入真核表达载体pcDNA3．1( )．测序正确的重组子pcDNA3．1-a(含GCRG213正向克隆), pcDNA3．1-b(含GCRG213反向克隆)和空载体经脂质体转染人胃癌细胞系MKN45细胞, G418筛选获得稳定转染的细胞株,采用半定量RT-PCR及Wlestern blot比较转染不同质粒的 MKN45细胞中GCRG213在mRNA和蛋白质水平上的表达差异．结果:经测序证实,GCRG213正向克隆和反向克隆正确插入真核表达载体 pcDNA3．1( ),组成重组子pcDNA3．1-a(含正向克隆),pcDNA3．1-b(含反向克隆)．重组子 pcDNA3．1-a,pcDNA3．1-b和空载体经脂质体转染人胃癌细胞系MKN45细胞,G418筛选获得稳定转染的细胞株．与对应的空载体比较,RT-PCR结果显示转染pcDNA3．1-a的 MKN45细胞中其mRNA的表达上调35．4％,而转染pcDNA3．1-b的MKN45细胞中其mRNA 的表达下调32．1％;Western blot结果显示转染 pcDNA3．1-a的MKN45细胞中其蛋白的表达上调49．4％,而转染pcDNA3．1-b的MKN45细胞中其蛋白的表达下调50．3％．结论:成功构建胃癌相关基因GCRG213正、反义真核表达载体．     

胃癌相关基因GCRG213真核表达载体的构建及其对胃癌细胞MKN45的影响

目的 研究胃癌相关基因GCRG213正义、反义转染对胃癌细胞MKN45的影响.方法 采用分子克隆及基因转染技术将GCRG213基因转入哺乳动物细胞,并结合反义转染技术研究GCRG213基因对胃癌细胞恶性生物学行为的影响.结果结果 GCRG213正向和反向克隆正确插人真核表达载体pcDNA3.1(+);重组子pcDNA3.1-a、pcDNA3.1-b和空载体转染人胃癌细胞系MKN45细胞;正义转染其mRNA的表达上调,而反义转染下调;正义转染加快MKN45细胞生长增殖速度、降低细胞凋亡率,反义转染减慢MKN45细胞生长增殖速度,增加细胞凋亡率.结论 胃癌相关基因GCRG213可促进肿瘤细胞生长、分裂和转移,抑制肿瘤细胞的凋亡,可能是一个新发现的恶性肿瘤癌变的促进因素.     

Role of nucleostemin in growth regulation of gastric cancer, liver cancer and other malignancies

AIM: To examine the role of nucleostemin in the growth regulation of gastric cancer, liver cancer and other cancers. METHODS: RT-PCR was used to clone the fragment of nucleostemin cDNA from HEK 293 cells. Eighteen kinds of malignant tumor tissues including gastric adenocarcinoma and liver cancer tissues, 3 kinds of benign tumor tissues, 3 kinds of benign hyperplastic tissues and normal tissues were employed to examine nucleostemin gene expression by RT-PCR, Slot blot, Northern blot and in situ hybridization. RESULTS: We successfully cloned a 570 bp fragment of nucleostemin-cDNA from HEK-293 cells. All detected malignant tumor tissues, benign tumor tissues, and benign hyperplastic tissues had high levels of nucleostemin expression. Nucleostemin was also expressed in human placenta tissue at a high level. In terminally differentiated normal human adult kidney and mammary gland tissues, no nucleostemin expression could be detected. CONCLUSION: Nucleostemin can help regulate the proliferation of both cancer cells and stem cells. It might play an important role in the growth regulation of gastric cancer, liver cancer and other cancers.     

肿瘤相关基因NAG6、NAG-7、BRD7在胃癌中的表达

目的　NAG6、NAG 7、BRD7为最近克隆的肿瘤相关新基因 ,对它们在胃癌及癌旁组织中的表达进行检测 ,探讨这些基因在胃癌发生发展中的作用。方法　采用RT PCR、Northern杂交、点杂交方法检测 34例胃癌和癌旁组织中这些基因的表达。结果　胃癌组织中 ,有 61 .8% (2 1 / 34)NAG6基因表达缺失 ,NAG6在胃癌组织中的表达较癌旁组织显著下调 (P <0 .0 1 ) ,但NAG6表达下调与胃癌淋巴结或远处转移无明显关系 (P >0 .0 5)。NAG 7基因在胃癌和癌旁组织中表达率分别为 88.2 % (30 / 34)和 82 .3 % (2 8/ 34)。BRD7基因在胃癌及癌旁组织中均有表达。RT PCR、Northern杂交、点杂交结果均显示NAG 7、BRD7基因在胃癌与癌旁组织之间的表达差异无显著性。同时 ,点杂交也证实NAG6在胃癌组织中表达下调。结论　NAG6基因在胃癌组织中表达显著下调 ,这可能在胃癌的发生发展过程中起重要作用 ,但可能与淋巴结或远处转移无关。BRD7、NAG 7基因在胃癌中未发现表达水平改变 ,初步提示这两种基因可能在胃癌的发生发展中不起作用     

Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer

PURPOSE: We have previously reported that EPHB2 is overexpressed in gastric cancer; however, the expression profiles of its ligands, EFNB1 and EFNB2, are unknown. This study was designed to investigate the expression of EPHB2 and its ligands, EFNB1 and EFNB2, in human gastric cancer. METHODS: Semi-quantitative RT-PCR using (32)P was performed on human gastric cancer tissues and corresponding normal tissues (29 gastric cancer patients). RESULTS: EPHB2 was more highly expressed in tumor tissues than in normal tissues in 21 out of 29 (72.4%), in gastric cancer patients ( P = 0.01); EFNB1 and EFNB2 were highly expressed in 21 out of 29 (72.4%) ( P = 0.037) and 14 out of 29 (48.3%) patients, respectively. The overexpression of EPHB2 was frequently detected in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma [10/13 (76.9%) and 9/14 (64.3%), respectively]. On the other hand, the overexpression of EFNB1 was more frequently detected in poorly differentiated adenocarcinoma than in well-differentiated adenocarcinoma [12/14 (85.7%) and 7/13 (53.8%), respectively. P =0.027]. Elevated levels of EPHB2 and EFNB1 were detected in substantial subsets of early gastric cancers. Genomic alterations to these three genes in gastric cancer specimens were either not found or rarely found except for several rare variations of EPHB2. CONCLUSIONS: These findings suggest that not only the expression of EPHB2, but the expression of its ligand EFNB1 may have some relation with the oncogenesis of gastric cancer.     

HTRA1 gene expression in gastric epithelial cells

Objective:To explore HtrA1 gene expression aud its regulation in human gastric cancers.Methods:The HtrA1 mRNA levels were examined by QPCR analysis and coufirmed its expression with Northern blot analysis.The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis.Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines.The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequeucing analysis.Effect of decitabine and TSA on HTRA1 expression in gastric cancer cell line was determined by RTPCR.Results:HIC analysis indicated that HtrA1 was highly expressed in normal epithelium,but dramatically down-regulated in gastric carcinoma tissues and variably expressed in tumor-adjacent tissues.HtrA1 gene expression was dramatically decreased in gastric carcinoma cells compared to nontumorigenic counterparts.The HtrA1 gene loss in any of the 4 breast cancer cell lines was not detected.Total 14 CpGs in this region were all methylated in gastric cancer cells,whereas two normal cells.GES-1 and HFI-145,were having several unmethylated cytosines in this region.HtrA1 showed as~Mr 44,000,Expression of HtrA1 protein was not observed in any of the four gastric caucer cell lines.BGC-823.MKN-45.SGC-7901and MKN-28.HtrA1 expression was observed in the HF1-145and GES-1 cell lines.Conclusions:The epigenetic silencing for HtrA1gene expression could provide a possible strategy for re-activating Htrt1 gene expression in gastric cancer cells.thus facilitating further investigation of HtrA1's role in chemotherapy.     

Expression of ST13 in colorectal cancer and adjacent normal tissues

AIM: To investigate the in situ expression of suppression of tumorigenecity 13 (ST13) mRNA in both colorectal cancer and adjacent normal tissues, METHODS: Colorectal cancer cell lines SW1116, SW620 and CoLo205 were enrolled to confirm the feasibility of the in situ hybridization procedure. Seven colorectal cancer and adjacent normal tissues were included for RNA-RNA in situ hybridization. RESULTS: The expression of ST13 in the seven normal colon tissues was positive and the positive signals appeared in mucosal cells. Only three of the seven colorectal cancer tissues had positive hybridization signals that appeared in adenocarcinoma cells. CONCLUSION: The expression of ST13 decreases in colorectal cancer tissue compared with that in adjacent normal tissue. ST13 is mostly expressed in colorectal epithelia and adenocarcinoma cells.